This invention relates to improved porous ceramic based biomaterials, and methods for making such materials, and implants fashioned therefrom. In particular, this invention relates to methods of impregnating porous hydroxyapatite with polymeric materials such that when the resultant composite materials are used in prosthetic devices and implants, strength of the implant is enhanced and the interconnected macropores are retained.
Porous Echinoderm and Scleractinian skeletal material has a unique carbonate structure. These materials are permeable with a uniform three dimensional, highly interconnected porosity. The microstructure of this material resembles cancellous bony tissue or bone. The similarity of these invertebrate skeletal materials in microstructure to bone makes them potentially highly useful as bone substitutes. Porites or Goniopera skeleton will resorb or degrade too rapidly to assure bone ingrowth. The natural carbonate skeletal materials, however, such as the calcite of Echinoid spine, or the aragonite skeletons are too brittle for many applications. This brittleness makes the natural carbonates particularly difficult to shape. They also lack the strength and durability required for some bone substitute applications.
A technique was developed to convert the aforementioned calcium carbonate materials into hydroxyapatite, while at the same time retaining the unique microstructure of the coral material. U.S. Pat. No. 3,929,971 (Roy) (incorporated herein by reference) discloses a hydrothermal exchange reaction for converting the porous carbonate coralline skeletal material into hydroxyapatite having the same microstructure as the carbonate skeletal starting material. These synthetic hydroxyapatite materials have been produced commercially for some time and are available from Interpore International, Irvine, Calif. under the trademark Interpore(copyright) Implant 200 (derived from coral of the genus Porites and having an average pore diameter of about 200 microns) and under the trademark ProOsteon(copyright) Implant 500 (derived from certain members of the family Goniopora and having an average pore diameter of about 500 microns).
Interpore(copyright) 200 and ProOsteon(copyright) Implant 500, also referred to as Replamineform hydroxyapatite and coralline hydroxyapatite, have been found to be useful as bone substitute materials in dental and surgical applications. These materials are essentially non-degradable, yet biocompatible, and resemble the microstructure of animal and human bone. The porosity of these coral derived materials has been characterized as polymodal by means of scanning electron microscope and mercury porosimetery. The macroporosity is characterized by macropores of 100-1000 xcexcm. The microporosity is characterized by spaces between crystallites on the order of 0.1 xcexcm and larger micropores on the order of 1 xcexcm. More information concerning these materials can be found in the article by Drs. Eugene W. White and Edwin C. Shors entitled xe2x80x9cBiomaterial Aspects of Interpore-200(copyright) Porous Hydroxyapatite,xe2x80x9d which appeared in Dental Clinics of North America, Vol. 30, January 1986, pp. 49-67, incorporated herein by reference. While calcium phosphates such as Interpore(copyright)200, and ProOsteon(copyright) Implant 500 are desirable for many applications, and promote the ingrowth of bone and other tissue into and around the implant, they do not satisfy all of the needs of surgeons using them as bone replacements or implants. U.S. Pat. No. 4,976,736 (White and Shors) (incorporated by reference) also discloses biomaterials useful for orthopedic and dental applications in which two rates of degradation are sought. To accomplish this, the inventors disclose a biomaterial (and method for making such a biomaterial) which has a base portion of calcium carbonate and a surface layer of calcium phosphate or hydroxyapatite. The biomaterial may be machined into various shapes and sizes for orthopedic and dental applications. The biomaterial presents an interface of hydroxyapatite to tissue and body fluids at the site of the surgical defect. The unreacted carbonate behind the interface gradually gets replaced by new bone ingrowth, thereby more completely filling the implant site with the body""s own bone material. In one embodiment mentioned in that patent, the macroporosity of the composite is filed with synthetic polymer such as polysulfone, polythylene, silicone rubber or polyurethane, either with positive injection pressure or by vacuum impregnation. After solification of the polymer, the carbonate may optionally be dissolved away with 10acetic acid, leaving behind the polymer that filled the pores.
Porous ceramics can also be manufactured using a variety of other methods. These ceramics, also made from calcium phosphates, can be used as bone graft substitutes. However, they also have mechanical limitations due to the porosity and to the brittle nature of ceramics. Some of these ceramics have microporosity in addition to macroporosity. Examples include U.S. Pat. Nos. 5,348,788; 5,455,100; and 5,487,933.
Tencer et al., in an article entitled, xe2x80x9cBone Ingrowth Into Polymer Coated Porous Synthetic Coralline Hydroxyapatite,xe2x80x9d J. Orth. Res. pp. 275-82 (1987), discusses dip-coating the macroporosity or large pores of a coralline hydroxyapatite sample with a polylactic acid (DL-PLA) dilactic-polylactic acid polymer by dipping blocks for 5 seconds in a high (3:1), medium (10:1), or low (30:1) viscosity solution of DL-PLA in chloroform.
The authors state that they achieved a three-fold increase in compressive strength over untreated samples. This treatment, however, tends to fill the macroporosity and obscures or fills the surface openings of the macropores, which limits the rate and amount of bone ingrowth.
An effective means of increasing the strength of coralline hydroxyapatite, while maintaining an open macroporosity for bone ingrowth, has yet to be described. It is therefore an object of the invention to provide bone substitute or implant materials derived from coral or synthetic calcium phosphate ceramics for bone incorporation which preserves the unique porous macrostructure and surface properties thereof, while providing increased strength.
The disadvantages of the foregoing prior biomaterials are overcome and the foregoing and other objects are achieved by providing an improved method for manufacturing a ceramic based biomaterial with polymer infiltrated micorpores. The process includes infiltrating the porous ceramic biomaterial with a monomer mixture or solution, and perhaps a catalyst if necessary, and treating the resulting material under conditions which cause the monomer to polymerize in situ within the microporosity of the biomaterial, thus strengthening the material and giving it other useful properties.
The invention also provides as a biomaterial a calcium phosphate (hydroxyapatite) structure having a substantially uniform three dimensional macroporosity connected with an interior surface of the biomaterial. The porosity includes interconnected macropores having diameters in the range from about 100 microns to about 1000 microns. The micorporosity of the ceramic biomaterial is infiltrated by a monomer or prepolymer, a catalyst if necessary, and then polymerized such that the polymer fills (or mostly fills) the microporosity of the biomaterial, substantially without filling the macropores therein. For example, monomers of DL-lactide, L-lactide, or glycolide or co-monomers thereof, at or above their melting point can infiltrate the microporosity of coralline hydroxyapatite materials, and then in the presence of a suitable catalyst be thermally polymerized in situ to yield composite materials of increased strength and durability. This is possible due to the low viscosity of the molten monomers combined with adequate capillary action of the microporous spaces. Using this method, strength increases of more than three-fold over the untreated material have been realized, without disrupting the necessary avenues for bone ingrowth.
In another aspect, the invention provides a method for making an improved biomaterial comprising the steps of providing a coralline calcium carbonate material and converting this material to a porous calcium phosphate (or hydroxyapatite) structure by reacting the calcium carbonate structure under heat and pressure in the presence of a synthetic phosphate; and strengthening the porous hydroxyapatite structure by suffusing the interstices of the microporosity with a monomer solution so that the monomer only lightly coats (but does not fill) the interior walls of the macroporosity of the porous hydroxyapatite structure, and then polymerizing the monomer, preferably in the presence of a catalyst.